Extensive rearrangement reactions observed for differently N-substituted 2,5-dimethylpyrroles under electron ionization

Abstract

The 70 eV electron ionization mass spectra of fourteen differently N-substituted 2,5-dimethylpyrroles were studied. In accord with the aromatic character of the pyrrole ring, all the compounds studied gave rise to an intense molecular ion peak. Regardless of the functional group at the 1-substituent, for all the compounds the principal fragmentation products were practically the same, although the relative peak intensities varied depending on the structure of the substituent. In addition, an amino group substituent prompted intense radical site initiated cleavages which were minor or totally absent with other compounds. The data showed that extensive rearrangement reactions took place. Some of these were seen directly from the mass spectra, and some only from closer examination of the ion structures. The structures of the ions at m/z 108 and 94, formally representing the [MÀ1]ions of 1,2,5-trimethylpyrrole and 2,5-dimethylpyrrole, respectively, were carefully studied using the collision induced dissociation (CID) technique. Measurements showed that ring expansion reactions took place, protonated 2,5-lutidine and protonated 2-picoline being the most likely isomers formed for the m/z 108 and 94 ions, respectively. The results obtained from the CID experiments were supported by semi-empirical calculations of heats of formation. # 1998 John Wiley & Sons, Ltd. Received 22 December 1997; Revised 5 January 1998; Accepted 10 January 1998 Rapid Commun. Mass Spectrom. 12, 231-238 (1998 A pyrrole ring is a part of many important biologically active compounds.1,2 In fact, some polysubstituted pyrroles have even been reported to have various biological and pharmaceutical activities.3,4 The condensation of diketones with primary amines constitutes a very useful method for generating pyrroles. This reaction is called the Paal-Knorr condensation, 5-7 and is described in Scheme 1.Unsubstituted pyrrole and its relatively simple alkylsubstituted derivatives have been studied by mass spectrometry to some extent. [8][9][10][11] In the present work, we synthesized fourteen differently N-substituted 2,5-dimethylpyrroles (listed below), by the Paal-Knorr condensation from 2,5-hexanedione and appropriate primary amines.The mass spectrometric behaviour of these compounds was studied under electron ionization. The main intention was to find the most important fragmentation routes of Nsubstituted pyrroles and the possible dependence of the fragmentation pathways and the nature of the substituent. The fragmentation routes were verified by exact mass measurements, metastable ion analysis and collision induced dissociation (CID) techniques. The spectra observed directly showed that several rearrangements take place. It is also known from the work of Glish et al.9 that ring expansion reactions are common with dimethylpyrroles. For these reasons, some detailed ion structural studies were carried out for long-lived ions generated from compounds 12 and 13, using a low energy CID technique. Heat of formation values were also calculated by a semiem...